Researchers at the National Institutes of Health (NIH) have developed a high-resolution digital replica of key eye cells, creating a powerful new platform to study how cellular organization breaks down in age-related macular degeneration (AMD), a leading cause of vision loss among people over 50.
The breakthrough modelling technology offers a detailed, three-dimensional view of retinal pigment epithelial (RPE) cells, which play a critical role in maintaining the health of light-sensing photoreceptors in the retina. Damage or death of RPE cells is a hallmark of AMD and eventually leads to irreversible vision loss.
Using advanced imaging and artificial intelligence, the researchers generated the first known subcellular-resolution digital twin of a differentiated human primary cell. The digital twin enables scientists to observe how healthy RPE cells organize themselves and how this organization deteriorates during disease, opening new avenues for therapeutic discovery.
The model was built using RPE cells derived from induced pluripotent stem cells developed by the Allen Institute for Cell Science. Researchers collected 3D imaging data from approximately 1.3 million RPE cells across nearly 4,000 fields of view using automated confocal microscopy.
Based on this dataset, the team trained an AI algorithm known as POLARIS (polarity organization with learning-based analysis for RPE image segmentation) to identify cell structures such as nuclei, mitochondria and cytoskeletal components, as well as overall cell shape and volume. The system generated detailed 3D segmentation data across multiple stages of cell development.
A central focus of the research was cellular polarity, a top-to-bottom organization that allows RPE cells to perform essential functions such as recycling photoreceptor components and transporting nutrients and waste. Analysis showed that healthy RPE cells follow a consistent developmental trajectory toward a polarized state, while disruptions in this process are linked to disease.
The resulting AI-driven atlas of polarized and non-polarized RPE cells provides a reference framework for studying AMD at cellular and subcellular levels. Researchers say the approach could significantly accelerate the development of new treatments and may be adapted to study other eye disorders and diseases beyond ophthalmology.
The study was funded by the NIH’s National Eye Institute (NEI) Intramural Research Program. NEI is the federal government’s lead agency for research on vision and eye diseases, supporting both basic and clinical studies aimed at preventing vision loss and improving quality of life for people with visual impairment.
